We propose to study the interaction of radiolabelled insulin and glucagon with isolated rat hepatocytes. The direct binding studies will be correlated with assay of amino acid transport, protein synthesis and adenyl cyclase activities. It is the goal of this study to determine whether insulin and glucagon binding is characterized by the presence of a slowly dissociable binding fraction similar to that which we have described for growth hormone. Accumulation of this fraction with time may be correlatable with loss of cellular sensitivity to applied hormone.